CNSPulse
W30

DIMENSIONS OF PSYCHEDELIC EXPERIENCE PREDICTING ANTIDEPRESSANT RESPONSE TO PSILOCYBIN ACROSS DIAGNOSES

Andrew van der Vaart — Jeffrey LaPratt2, Kimberly Swartz2, Audrey Shoultz2, Margo Lauterbach2, Trisha Suppes3, Harold Sackeim4, Scott Aaronson1 1Sheppard Pratt Health System and University of Maryland School of Medicine, 2Sheppard Pratt Health System, 3Stanford University, 4College of Physicians and Surgeons, Columbia University

2026 ASCP Annual Meeting

Introduction

Psilocybin therapy has demonstrated efficacy for Major Depressive Disorder (MDD) and Bipolar Depression, yet the mechanisms predicting therapeutic response remain under investigation. We examined whether features of the psychedelic experience, according to the 5 dimensions of Altered States of Consciousness (5D-ASC), predict antidepressant outcomes across a transdiagnostic cohort.

Methods

Adults (N=45) with MDD with severe treatment resistance, Bipolar II Depression, or MDD with chronic Suicidal Ideation received a single 25mg dose of psilocybin across arms of an open-label trial. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at Baseline and Week 3. The 5D-ASC was administered immediately post-dosing. Pearson correlations assessed associations between 5D-ASC dimensions and the change in MADRS scores.

Results

An overall significant association was found between the Oceanic Boundlessness (OB) dimension and reduction in depression severity (r = -0.34, p = 0.02. Visionary Restructuralization (VR) showed a trend toward significance (r = -0.29, p = 0.054). Baseline depression severity and other ASC dimensions (Anxious Ego Dissolution, Auditory Alterations) were not predictive of outcome.

Conclusion

These findings suggest that the dimension of “Oceanic Boundlessness” during psychedelic experience predicts therapeutic response to psilocybin for depression, independent of baseline symptom severity and regardless of primary mood disorder. Future controlled trials should further explore this relationship to optimize patient selection and dosing strategies.